Lecture 8.1: Gestational and Placental Disorders Flashcards
Spontaneous abortion (aka miscarriage) is defined as pregnancy loss before ______ weeks of gestation
20 weeks of gestation (most often occurs before week 12)
What are 2 common fetal chromosomal anomalies associated with spontaneous abortion?
Turner Syndrome (45, XO) and trisomy 16
What are some maternal endocrine factors which may lead to spontaneous abortion?
- Luteal-phase defect
- Poorly controlled diabetes
Which systemic disorder of the vascular is associated with spontaneous abortions and a false positive syphilis test?
Antiphospholipid antibody syndrome
What is the most important predisposing condition (35-50%) for ectopic pregnancy?
Chronic salpingitis secondary to PID –> intralumenal fallopian tube scarring
What are some of the risk factors for ectopic pregnacy?
- Chronic salpingitis secondary to PID
- Scarring of fallopian tubes due to: appendicits, endometriosis, and/or prior surgery
- IUD use = 2x ↑ risk
- Smoking
Why is it important to recognize a potential ectopic pregnancy?
- Rupture of tubal pregnancy = emergency!
- May lead to intraperitoneal hemorrhage –> hemorrhagic shock –> DEATH!
Diagnosis of ectopic pregnancy is based on what?
- ↑ serum levels of hCG
- Pelvic sonography
- Endometrial biopsy showing decidua w/o chorionic villi or implantation site
- Laparoscopy
Typical clinical presentation of ectopic pregnancy?
Onset of moderate-severe abdominal pain + vaginal bleeding 6-8 weeks after last menstrual period
What are the 3 basic types of twin placentas?
- Diamnionic dichorionic (may be fused)
- Diamnionic monochorionic
- Monoamnionic monochorionic
Twin-twin transfusion syndrome is a complication of what type of twin placenta; what occurs in this syndrome?
- Complication of monochorionic twin pregnancy
- Monochorionic placentas have vascular anastomoses that connect the circulation of each fetus; sometimes including one or more AV shunts
- Shunt preferentially ↑ blood flow to one twin (polyhydramnios) at expense of other (oligohydramnios)
What is the placenta previa; leads to what complications?
- Placenta implants in lower uterine segment or cervix, often leads to serious 3rd trimester bleeding
- Complete placenta previa covers internal cervical os and requires delivery via C-section
What is placenta accreta; leads to what complication?
- Partial or complete absence of the decidua, such that placental villous tissue adheres directly to myometrium
- Leads to failure of placental separation at birth —> important cause of severe, life-threatening postpartum bleeding
Which pathway is the most common for placental infections and is caused by what?
Ascending infections caused by bacteria i.e., Gonorrhea and Chlamydia
Preeclampsia is what type of syndrome and due to dysfunction of what?
SYSTEMIC syndrome due to endothelial dysfunction
What is the triad of preeclampsia?
- HTN (endothelial dysf. –> vasoconstriction)
- Edema (↑ vascular permeability)
- Proteinuria (↑ vascular permeability)
Development of what makes preeclampsia become eclampsia?
Develop hyperreflexia and convulsions
Preeclampsia usually occurs in what trimester and which women are at greater risk?
- Third trimester (after 34 weeks gestation)
- Most common in primiparas (women pregnant for 1st time)
How is preeclampsia distinguished from gestational HTN?
Gestational HTN lacks proteinuria
Some women w/ severe preeclampsia can develop HELLP syndrome, which stands for what?
- Microangiopathic Hemolytic anemia
- _E_levated _L_iver enzymes
- _L_ow _p_latelets
Abnormal placental vasculature formation as part of the pathogenesis of preeclampsia is due to what 2 major events?
- Abnormal trophoblastic implantation
- Failure of physiologic remodeling of the maternal vessels
In response to hypoxia the ischemic placenta releases what 2 placenta-derived antiangiogenic factors into maternal circulation and what does each antagonize the effects of?
- soluble FMS-like tyrosine kinase (sFltl) antagonizes VEGF
- Endoglin antagonizes TGF-β
Preeclampsia is associated with a hypercoagulable state that may lead to formation of thrombi in the arterioles and capillaries of what main sites?
Liver + kidneys + brain + pituitary
Hypercoagulablity in preeclampsia is related to what factors?
- ↓ endothelial prod. of PGI2 (potent antithrombic factor)
- Prod. of PGI2 is normally stimulated by VEGF, which is being antagonizd by sFlt1
What 4 microscopic changes are seen in the placenta in women with preeclampsia?
- Infarcts, which are larger and more numerous
- Exaggerated ischemic change of chorionic villi and trophoblasts, consisting of ↑ syncytial knots***
- Frequent retroplacental hematomas
- Abnormal decidual vessels w/ thrombi, fibrinoid necrosis, or intraintimal lipid deposits (acute atherosis)**
When liver lesions are present with preeclampsia what is seen?
- Intraparenchymal hemorrhage
- Fibrin thrombi in portal capillaries and foci of hemorrhagic necrosis
What are the features of kidney lesions associated with preeclampsia, specifically the glomeruli?
- Swelling of endothelial cells
- Amorphous dense deposits on endothelial side of BM
- Mesangial cell hyperplasia
What will immunofluorescent studies of the kidney in preeclampsia show an abundance of?
Fibrin in glomeruli
Preeclampsia will present earlier (before 34 weeks gestation) in women w/ what 4 underlying conditions?
- Hydatidiform mole
- Preexisting kidney disease
- HTN
- Coagulopathies
Which sx’s assoc. w/ preeclampsia are serious events indicative of severe preeclampsia often requiring delivery?
Headaches and visual disturbances
How is preeclampsia managed based on gestational age and severity?
- Term pregnancies, delivery is tx of choice, regardless of severity
- Pre-term requires close monitoring; if severe sx’s arise, delivery is indicated regardless of gestational age
- Anti-HTN’s do NOT improve outcomes!!!
What are some of the possible long-term complications of mother who had preeclampsia?
- 20% develop HTN and microalbuminuria within 7 years of pregnancy
- 2x ↑ risk of vascular disease of heart and brain
The diagnosis of acute fatty liver of pregnancy rests on biopsy showing what?
Diffuse microvesicular steatosis of hepatocytes
Pathogenesis of acute fatty liver of pregnancy is due to what type of dysfunction?
- Mitochondrial; fetus produces metabolites that cannot be broken down by mother
- Deficiency of mitochondrial long-chain 3-hydroxyacyl CoA dehydrogenase
In preeclampsia/eclampsia, what catastrophic event may happen to blood under pressure inside the liver?
Coalesce and expand to form hepatic hematoma; dissection of blood under Glisson capsule —> catastrophic hepatic rupture
Why are Hydatidiform moes important to recognize?
Assoc. w/ ↑ risk of persistent trophoblastic disease (invasive mole) or choriocarcinoma
Hydatidiform moles are characterized histologically by what?
Cystic swelling of the chorionic villi accompanied by variable trophoblastic proliferation
When and how are Hydatidiform moles usually diagnosed; there is an ↑ risk in which age groups?
- Diagnosed early in preg. (average 9 weeks) by sonogram (US)
- ↑ incidence in teens and btw 40-50 y/o
Hydatidiform moles are more common in what part of the world?
2x more common in Southeast Asia
What does a complete mole result from and what are the karyotypes seen?
- Fertilization of an egg that has lost its female chromosomes; as result genetic material is completely paternally derived
- 90% = 46,XX from duplication of genetic material from one sperm
- NO fetal tissue
What occurs in a Partial mole and what is the resultant karyotype?
- Fertilization of an egg with 2 sperm
- Karyotype = triploid (i.e., 69,XXY) or tetraploid (i.e., 92,XXXY)
How do complete moles differ from partial moles in terms of presence of fetal tissue and risk of future complications?
- Complete moles ↑ risk for choriocarcinoma and persistent or invasive mole; no fetal tissue
- Partial moles will usually have fetal tissue present; are not associated with choriocarcinoma
What is the classic morphological appearance of hydatidiform moles?
Delicate, friable mass of thin-walled, translucent, cystic, grapelike structure w/ swollen edematous (hydropic) villi
Most women with partial and early complete moles present how?
- Spontaneous miscarriage
or
- Undergo curettage because of US findings of abnormal villous enlargment
Levels of what will be greatly increased with complete moles and this level can be used to monitor for successful removal?
β-hCG levels
Continous elevation of β-hCG after removal of a hydatiform mole likely indicates what?
Persistent or Invasive mole
Invasive hydatidiform moles are characterized by invasion where and what events follow?
- Penetration or perforation of uterine wall; invasion of myometrium by hydropic chorionic villi
- Proliferation of both cyto- and syncytiotrophoblasts
- Tumor is locally destructive and may invade parametrial tissue and blood vessels –> hydropic villi may embolize to sites, such as lung and brain
What are signs/sx’s and tx for invasive mole?
- Vaginal bleeding + irregular uterine enlargement
- Responds to chemo but may result in uterine rupture and necessitate hysterectomy
What is a choriocarcinoma, which cells are involved and is it benign or malignant?
- Malignant neoplasm of trophoblastic cells derived from previously normal or abnormal pregnancy
- Rapidly invasive and metastasize widely, but responds well to chemo
List 4 conditions which most often precede development of choriocarcinoma?
- 50% arise in complete mole
- 25% arise in previous abortion
- 22% after normal pregnancy
- Remainder in ectopic pregnancy
How does choriocarcinoma appear grossly?
Soft, fleshy, yellow-white tumor w/ large pale areas of necrosis and extensive hemorrhage
What is the typical presentation of a choriocarcinoma?
- Irregular vaginal spotting of bloody, brown fluid
- Sometimes sx’s don’t arise until months after preceding event
- hCG is typically ↑↑↑, unless tumor is necrotic they may be low
Choriocarcinoma has a high propensity for what route of spread and what are the most common site of metastasis?
- Hematogenous
- Lungs (50%) and vagina (30-40%)l followed by brain > liver > bone and kidney
What is the tx for choriocarcinoma and the prognosis?
- Depends on stage and usually consists of evacuation of the uterus contents + chemotherapy
- Nearly 100% remission and high cure rate w/ chemotherapy
Placental site trophoblastic tumor is composed of what cells?
Neoplastic proliferation of extravilous trophoblasts (aka intermediate trophoblasts)
Which hormone is produced by normal extravillous trophoblasts and may be ↑ in placental site trophoblastic tumor?
Human placental lactogen (hPL)
Histologically what is seen with placental site trophoblastic tumors?
Malignant trophoblastic cells diffusely infiltrating the endomyometrium
